背景: 泌尿道移行細胞癌經常是多發性的，多發性腫瘤的形成可能藉由腔內播種，此類多發性腫瘤一般都源自同一個惡性細胞。另一個多發性形成的原因是尿液中的致癌物，造成整個泌尿上皮的癌化，形成多個獨立不同來源的腫瘤。多發性泌尿道移行細胞癌可以來自腔內播種或整個泌尿上皮的癌化，然而這兩種不同成因的多發性腫瘤，其臨床表現則少有人探討。
方法: 利用來自上皮的癌化的兩側上泌尿道移形細胞癌，與來自腔內播種的上泌尿道腫瘤之後發生的膀胱癌，來判斷多發性泌尿上皮癌來自腔內播種或上皮癌化這兩者，在腫瘤的復發、進展與預後有無不同。
結果: 兩側上泌尿道上皮癌為上皮癌化所造成，其臨床表現較來自腔內播種的膀胱癌侵犯性強且預後差，並且經常合併腎功能異常。
結論: 多發性泌尿道移行細胞癌若來自整個泌尿上皮的癌化，其臨床表現應該與來自腔內播種者不同。

BACKGROUND: An important characteristic of transitional cell carcinoma (TCC) is the formation of tumors in multiple sites throughout the whole urinary tracts. Two theories explain the pathophysiologic mechanisms of multifocal tumors: (1) intraluminal seeding, it indicates the multiple tumors come from a single transformed malignant cell with secondary seeding or migration at different sites, and (2) the field cancerization, carcinogens affect the urothelium at multiple sites, leading to numerous mutation and independent growth of multifocal polyclonal tumors. Multifocal urothelial carcinomas could come from intraluminal seeding or from field cancerization. However, the data of clinical behaviors between the two different tumor types are lacking.
METHODS: Bilateral synchronous and metachronous primary TCC of the upper urinary tracts were derived from field cancerization. Recurrent bladder cancers following upper-tract tumors mostly come from intraluminal seeding. The recurrence, progression, and prognosis of the two different tumors were analyzed.
RESULTS: Bilateral upper-tract urothelial carcinomas derived from field cancerization were frequently associated with renal insufficiency, which were more invasive and had poor prognosis than bladder tumors derived from intraluminal seeding.
CONCLUSION: The clinical behaviors of the multiple urothelial tumors derived from field cancerization and from intraluminal seeding should be different.

中文摘要
Abstract
Abbreviation
Chapter 1. Introduction
Chapter 2. The Development of Bladder Tumors and Contralateral Upper Urinary Tract Tumors after Primary Transitional Cell Carcinoma of the Upper Urinary tract
2.1 Materials and Methods
2.2 Results
2.3 Discussion
Chapter 3. Synchronous Bilateral Primary Transitional Cell Carcinoma of the Upper Urinary Tracts
3.1 Materials and Methods
3.2 Results
3.3 Discussion
Chapter 4. Conclusion
References

References
1. Hafner C, Knuechel R, Stoehr R, et al: Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies. Int J Cancer 2002; 101: 1-6.
2. Takahashi T, Kakehi Y, Mistsumori K, et al: Distinct microsatellite alternations in upper urinary tract tumors and subsequent bladder tumors. J Urol 2001; 165: 672-677.
3. Hafner C, Knuechel R, Zanardo L, et al: Evidence for oligoclonality and tumor spread by intraluminal seeding in multifocal urothelial carcinomas of the upper and lower urinary tract. Oncogene 2001; 20: 4910-4915.
4. Takahashi T, Habuchi T, Kakehi Y, et al: Clonal and chronological gentic analysis of multifocal cancer of the bladder and upper urinary tract. Cancer Res 1998; 58: 5835-5841.
5. Habuchi T, Takahashi R, Yamada H, et al: Metachronous multiple development of urothelial cancers by intraluminal seeding. Lancet 1993; 342: 1087-1088.
6. Nakamura K, Fujiyama C, Tokuda Y, et al: Bladder cancer cell implantation in reconstructed bladder in vitro: a model of tumor recurrence. BJU Int 2002; 89: 119-125.
7. Cosyns JP, Jadoul M, Squifflet JP et al: Urothelial lesions in Chinese-herb nephropathy. Am J Kidney Dis 1999; 33: 1011-1017.
8. Nortier JL, Martinez MC, Schmeiser HH et al: Urothelial carcinoma associated with the use of a Chinese-herb (Aristolochia fangchi). N Engl J Med 2000; 342: 1686-1692.
9. Krogh J, Kvist E, Rye B: Transitional cell carcinoma of the upper urinary tract: prognosis variables and post-operative recurrences. Br J Urol 1991; 67: 32-36.
10. Hatch TR, Hefty TR, Barry JM: Time-related recurrence rates in patients with upper tract transitional cell carcinoma. J Urol 1988; 140:40-41.
11. Mufti GR, Gove JRW, Badenoch DF, et al: Transitional cell carcinoma of the renal pelvis and ureter. Br J Urol 1989; 63: 135-140.
12. Chou TH, Huang CH: Unusual clinical presentation of upper urothelial carcinoma in Taiwan. Cancer 1999; 85: 1342-1344.
13. Chen CJ, Chung C, Lin TM, et al.: Malignant neoplasms among residents of blackfoot disease endemic area in Taiwan: high-arsenic artesian well water and cancers. Cancer Res 1985; 45:5895-5899.
14. Chiang HS, Hong CL, Guo HR, et al.: Comparative study on the high prevalence of bladder cancer in the blackfoot disease endemic area in Taiwan. J Formos Med Assoc 1998; 87: 1074-1080.
15. Chiang PH, Huang MS, Tsai CJ, et al: Transitional cell carcinoma of the renal pelvis and the ureter in Taiwan: DNA analysis by flow cytometry. Cancer 1993; 71: 3988-3992.
16. Lee SH, Lin JS, Tzai TS, et al: Prognostic factors of primary transitional cell carcinoma of the upper urinary tract. Eur Urol 1996; 29: 266-271.
17. Yang MH, Chen KK, Yen CC, et al: Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urol 2002; 59: 681-687.
18. Leder RA, Dunnick NR: Transitional cell carcinoma of the pelvicalices and ureter. AJR 1990; 155: 713-722.
19. Millis C, Vaughan ED. Carcinoma of the ureter: natural history, management, and 5-year survival. J Urol 1983; 129: 275-277.
20. Tawfiek ER, Bagley DH: Upper-tract transitional cell carcinoma. Urol 1997; 50: 321-329.
21. Nielsen K, Ostri P: Primary tumors of the renal pelvis: evaluation of clinical and pathological features in a consecutive series of 10 year. J Urol 1988; 140: 19-21.
22. Charbit L, Gendreau MC, Mee S, et al.: Tumors of the upper urinary tract: 10 years of experience. J Urol 1991; 146: 1243-1246.
23. Racioppi M, Daddessi A, Alcini A, et al.: Clinical review of 100 consecutive surgically treated patients with upper urinary tract transitional tumours. Br J Urol 1997; 80: 707-711.
24. Badalament RA, Otoole RV, Kenworthy P, et al: Prognostic factors in patients with primary transitional cell carcinoma of the upper urinary tract. J Urol 1990; 144: 859-863.
25. Hisataki T, Miyao N, Masumori N, et al: Risk factors for the development of bladder cancer after upper tract urothelial cancer. Urology 2000; 55:63-67.
26. Lord GM, Cook T, Arlt VM, et al: Urothelial malignant disease and Chinese herbal nephropathy. Lancet 2001; 358: 1515-1516.
27. Dennis MJ, Ryan JJ, and Bishop MC: Renal transplantation in a patient with multifocal transitional cell carcinoma. Br J Urol 1993; 72: 383-384.